Phase I Trial of QH-1A Hybrid Bio-Artificial Liver With Ex Vivo Blood-Purifying MSCs in Acute-on-Chronic Liver Failure

NCT06996392 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: PL20
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this Phase I clinical trial is to evaluate the safety and efficacy of combining the QH-1A bioartificial liver device with mesenchymal stem cells（MSCs） for blood purification in treating patients with acute-on-chronic liver failure, and to determine the optimal treatment duration and frequency for Phase II. The study will enroll patients aged 18 to 65 years who meet the diagnostic criteria for acute-on-chronic liver failure as outlined in the 2024 Chinese Liver Failure Clinical Guidelines. The main questions this study aims to answer are:

• Does the combined therapy improve the 28-day survival rate after the final treatment?
• Does the QH-1A device in its HBAL mode consistently achieve the predefined device performance pass rate?
• Do patients show significant improvements in their biochemical markers following treatment?
• What is the immunogenicity profile of the mesenchymal stem cells used for blood purification? Participants will be screened within 14 days before their first treatment and will be allocated into one of four groups based on treatment duration and frequency:
• 4-hour group (3 patients)
• 6-hour group (3 patients)
• 8-hour group (3 patients)
• Multiple-treatment group (6 patients) Treatment will be administered in a sequential escalation-from the 4-hour group up to the multiple-treatment group-based on safety data from a 28-day observation period, which will be reviewed by a Safety Evaluation Committee. In addition, upon referral to the Hepatitis B Health Clinic, participants will receive tailored health education, comprehensive liver function and virological assessments, and an individualized treatment and follow-up plan.

Conditions

Acute-On-Chronic Liver Failure

Keywords

Acute -On-Chronic Liver Failure; Bio-artificial liver; Mesenchymal stem cells

Outcome Measures

Primary Outcomes (1)

• Survival rate

  28-day

Secondary Outcomes (5)

• Combined Bioartificial Liver Device QH-1A Equipment Performance Pass Rate

  Day 1

• Changes from the baseline in Child-Pugh grade

  28-day

• Changes from the baseline in COSSH-ACLF IIs

  28-day

• Changes from the baseline in MELD score

  28-day

• The rate of bridging liver transplantation

  28-day

Other Outcomes (5)

• Incidence of adverse events and serious adverse events

  28-day

• Number of participants with positive infectious pathogens in the return fluid

  Day1

• Number of participants with positive replicative lentivirus in the blood

  Day1,Day28

Study Arms (4)

4-hour group

EXPERIMENTAL

The 4-hour group will receive a single biological artificial liver treatment for 4 hours (±15 minutes).

Combination Product: Combining the QH-1A bioartificial liver device with mesenchymal stem cells for blood purification（4 hours）

6-hour group

EXPERIMENTAL

The 6-hour group will receive a single biological artificial liver treatment for 6 hours (±15 minutes).

Combination Product: Combining the QH-1A bioartificial liver device with mesenchymal stem cells for blood purification（6 hours）

8-hour group

EXPERIMENTAL

The 8-hour group will receive a single biological artificial liver treatment for 8 hours (±15 minutes).

Combination Product: Combining the QH-1A bioartificial liver device with mesenchymal stem cells for blood purification（8 hours）

Multiple-treatment group

EXPERIMENTAL

The Safety Evaluation Committee will determine the maximum tolerable treatment duration based on the 28-day safety observation outcomes from the 4-, 6-, and 8-hour groups. This duration will then be adopted as the treatment time for the multiple-treatment group. Subjects in the multiple-treatment group will undergo 2-3 treatments at this maximum duration, with an interval of 3 (±1) days between sessions.

Combination Product: Combining the QH-1A bioartificial liver device with mesenchymal stem cells for blood purification（Multiple-treatment）

Interventions

Combining the QH-1A bioartificial liver device with mesenchymal stem cells for blood purification（4 hours） COMBINATION_PRODUCT

The 4-hour group treatment session lasts 4 hours (±15 minutes). In the HBAL mode of the combined bioartificial liver device QH-1A, blood is initially filtered to separate the plasma, which is then pumped into a bioreactor. In this study, this bioreactor is uniquely filled with immortalized mesenchymal stem cells (PT-MSCs) optimized for blood purification. These cells are cultured to adhere to the outer surface of hollow fibers within the bioreactor, creating a stable and efficient living interface that continuously secretes bioactive factors such as exosomes.After passing through the bioreactor, the plasma is re-filtered and then returned to the patient's circulation via a dedicated pump.

4-hour group

Combining the QH-1A bioartificial liver device with mesenchymal stem cells for blood purification（6 hours） COMBINATION_PRODUCT

After the three subjects in the 4-hour group completed their 4-week follow-up, the Safety Evaluation Committee convened a meeting to review the safety data and determine whether to proceed with the recruitment for the 6-hour group.The 6-hour group treatment session lasts 6 hours (±15 minutes).The treatment procedure is identical to that of the 4-hour group.

6-hour group

Combining the QH-1A bioartificial liver device with mesenchymal stem cells for blood purification（8 hours） COMBINATION_PRODUCT

After the three subjects in the 6-hour group completed their 4-week follow-up, the Safety Evaluation Committee convened a meeting to review the safety data and determine whether to proceed with the recruitment for the 8-hour group. The 8-hour group treatment session lasts 8 hours (±15 minutes).The treatment procedure is identical to that of the 4-hour group.

8-hour group

Combining the QH-1A bioartificial liver device with mesenchymal stem cells for blood purification（Multiple-treatment） COMBINATION_PRODUCT

Subjects in the multiple-treatment group will receive 2-3 sessions of bioartificial liver treatment; the number of sessions will be determined by the investigators based on the subjects' clinical needs. The treatment duration for each session will be set as the maximum tolerable period, as confirmed by the Safety Evaluation Committee based on 28-day safety observations from the 4-hour, 6-hour, and 8-hour groups. Each treatment session is administered following the procedure applied to patients in the group with the optimal tolerability duration.

Multiple-treatment group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 65 years, irrespective of gender.
• Patients with acute-on-chronic liver failure, diagnosed according to the - - Guideline for diagnosis and treatment of liver failure (2024 version) in China.
• Subjects must provide informed consent prior to the study and voluntarily sign the written informed consent form.
• Subjects must be able to communicate effectively with the investigators and comply with the study protocol.

You may not qualify if:

• Active bleeding or disseminated intravascular coagulation (DIC) that is not effectively controlled.
• Allergies to the blood products or medications used during treatment.
• Circulatory failure.
• Occurrence of myocardial infarction, cerebral infarction, or cerebral hemorrhage within the past 6 months.
• A history of malignant tumors within the past 5 years (except for cured basal cell carcinoma of the skin or carcinoma in situ of the cervix).
• Any other conditions that, in the opinion of the investigator, render the subject unsuitable for participation in the study.

Sponsors & Collaborators

• Third Affiliated Hospital, Sun Yat-Sen University: lead
• Guangdong Qianhui Biotechnology Co., Ltd: collaborator

Study Sites (1)

Third Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510630, China

Location

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 11, 2025
• First Posted: May 30, 2025
• Study Start: May 7, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)